Peripheral T lymphocytes from rheumatoid arthritis patients recognize determinants on light chains and/or Fab fragments of immunoglobulin G.
Peripheral blood T lymphocytes from 29 of 31 patients with rheumatoid arthritis incorporated significant quantities of thymidine when cultured with pooled human immunoglobulin G (IgG). In contrast to the observation of general reactivity to pooled Igg, responses to pooled IgM were rare (3 of 26 patients). None of 11 controls responded to either IgG or IgM. Response to IgG is maximal on day 6 of culture and is dependent on concentration of IgG. The responding cells recognize determinants on monoclonal light chains and/or Fab fragments. Response to light chains follows one of three patterns: preferential response to lambda chains, preferential response to kappa chains, and essentially equal response to either kappa of lambda chains.


P3HT:Bebq2-Based Photovoltaic Device Enhances Differentiation of hiPSC-Derived Retinal Ganglion Cells.
Electric field stimulation is known to affect various cellular processes, including cell fate specification and differentiation, particularly towards neuronal lineages. This makes it a promising therapeutic strategy to stimulate regeneration of neuronal tissues. Retinal ganglion cells (RGCs) is a type of neural cells of the retina responsible for transduction of visual signals from the retina to the brain cortex, and is often degenerated in various blindness-causing retinal diseases. The organic photovoltaic materials such as poly-3-hexylthiophene (P3HT) can generate electric current upon illumination with light of the visible spectrum, and possesses several advantageous properties, including light weight, flexibility and high biocompatibility, which makes them a highly promising tool for electric stimulation of cells in vitro and in vivo. In this study, we tested the ability to generate photocurrent by several formulations of blend (bulk heterojunction) of P3HT (which is electron donor material) with several electron acceptor materials, including Alq3 and bis(10-hydroxybenzo[h]quinolinato)beryllium (Bebq2). We found that the photovoltaic device based on bulk heterojunction of P3HT with Bebq2 could generate photocurrent when illuminated by both green laser and visible spectrum light. We tested the growth and differentiation capacity of human induced pluripotent stem cells (hiPSC)-derived RGCs when grown in interface with such photostimulated device, and found that they were significantly increased. The application of P3HT:Bebq2-formulation of photovoltaic device has a great potential for developments in retinal transplantation, nerve repair and tissue engineering approaches of treatment of retinal degeneration.


Determination of dietary habits as a risk factor of cardiovascular heart disease in Turkish adolescents.
To investigate dietary habits and evaluate these with regard to cardiovascular risk status in Turkish adolescents aged 12-19 years. A total of 300 adolescents, 135 males and 165 females aged between 12 and 19, were included in the study. Dietary intake was determined by using 3-day food records (including 1 weekend day). Adolescents' smoking habits and familial chronic diseases were recorded. The values obtained for energy and nutrient intakes were compared with RDA and DRI and recommendations given by AHA. The mean energy intakes of male and female subjects were 1964 +/- 723 kcal and 1804 +/- 486 kcal respectively. According to NHANES III, age-standardized (CDC: Centers for Disease Control and Prevention) prevalence of overweight indicated that 20.7% among male and 17.5% among female adolescents were at risk for becoming overweight. The prevalence of premature CHD family history was found to be 9.6% for males and 11.5 % for females. The prevalence of current smoking was found to be 22.2 % for males and 18.2 % for females. In addition, 29.6% of the males and 37.6% of the females were physically inactive (p < 0.05); however, male adolescents (48.2%) were significantly more likely than female adolescents (52.1 %) to report sufficient moderate physical activity (p < 0.05). The dietary fiber intake was slightly below the recommended intake of 10 g per 1000 kcal. Compared to the AHA averages, these adolescents had significantly higher intake of total fat, saturated fat, sodium and dietary cholesterol and lower intake of polyunsaturated fat, monounsaturated fat and dietary fiber. The Turkish adolescents also had higher amounts of energy from fat. The mean percentage of energy from fat was 34.2 +/- 6% TE for males and 35.2 +/- 6.8 % TE for females; saturated fat was 11.8 +/- 6.8 % TE for males and 12.1 +/- 8.9 for females. The intake of fat and saturated fat was higher than the AHA recommendations. The polyunsaturated to saturated fat ratio was 0.4 +/- 0.2 and reflected a high saturated fat (12.0 +/- 7.7% TE) and low polyunsaturated fat (5.5 +/- 3.9 % TE) diet. In addition, the percentage of adolescents who did not meet 66% of RDA for vitamin E, B6, and folates and the recommendation for RDA dietary fiber is presented. Approximately, 80% of adolescents failed to meet the dietary recommendation of the AHA for polyunsaturated fatty acids, and about 26.7% reported a cholesterol intake higher than 100 mg/1000 kcal. It can be said that fiber, total fat, saturated fatty acid, cholesterol and sodium intake of Turkish adolescents are found to be high; however, their vitamin E, vitamin B6 and folate intake are found to be low compared to AHA recommendations. Turkish adolescents' fruit and vegetable intake are also found to be low.


Characteristics, management, and in-hospital mortality of acute myocardial infarction in the "real world" in France--data from a large unselected cohort of 2,519 consecutive patients in a French region.
The prospective PRIMA study (Prise en charge de l'Infarctus du Myocarde Aigu; management of acute MI) sought to determine characteristics, management, and in-hospital mortality of myocardial infarction (MI), regardless of age and hospital facilities, in the "real world" in a region in France. Data were prospectively collected in all patients with MI admitted in all hospitals in three departments in the Rh ne-Alpes region between September 1, 1993 and January 31, 1995. 2,519 patients (68% men; mean +/- SD: 68 +/- 14 years) were included. Time from onset of symptoms to admission was < 6 h in 56% of the patients (median: 4 h 30 min). MI was non-Q wave in 12%. Among Q wave MI, location was anterior in 44%. At admission, Killip class was > 1 in 33%. The overall rate of thrombolysis was 36%. It was significantly higher in men than in women, in younger patients than in older patients, in lower Killip classes, in Q wave MI, and when the delay before initial medical intervention was < 6 hours. After age-adjustment, there was no difference between men and women for thrombolysis rate (odds ratio women/men: 0.92; p = 0.10). During the first 5 days, Killip class worsened in 17%. In-hospital mortality rate was 14%. Multivariate analysis identified age, anterior location, presence of Q waves, and higher Killip classes as significant predictors of in-hospital mortality. This large unselected cohort revealed that among patients with MI in a French region, there was a high proportion of elderly patients, a low rate of thrombolysis, and a high in-hospital mortality.


Tubal Ligation Induces Quiescence in the Epithelia of the Fallopian Tube Fimbria.
Tubal ligation keeps the fimbriated end of the fallopian tube intact while interrupting the conduit for sperm and egg between the uterus and ovary. Tubal ligation is associated with an approximately 20% decreased risk of high-grade serous ovarian cancers, which mounting evidence suggests arise from the distal fallopian tube epithelium. We postulated that biological changes at the epithelial cellular level of the distal fallopian tube may account for the surgical procedure's observed risk reduction. We compared the histology, presence of epithelial progenitors (basally located CD44-positive cells), and degree of epithelial proliferation (Ki67-positive cells) of distal fallopian tube from 10 patients with previous tubal ligation and 10 age-matched patients with uncut fallopian tubes. A significantly reduced population of proliferating epithelial progenitors (basally located CD44/Ki67 dual-positive cells) was detected in the tubal ligated specimens (P = .0002). To functionally assess the effect of tubal ligation, a murine model was utilized to compare the growth capacity of distal fallopian tube epithelial cells isolated from either ligated or sham-operated tubal epithelia. Murine fallopian tube epithelial cells isolated after tubal ligation showed a significantly reduced capacity to grow organoids in culture compared to sham-operated controls (P = .002). The findings of this study show that tubal ligation is associated with a reduced presence and decreased proliferation of progenitor cells in the distal fallopian tube epithelium. These compositional and functional changes suggest that tubal ligation induces quiescence of distal fallopian tube epithelial cells.


Overcoming the Impedance Range Limitations of Portable Bioelectrical Impedance Spectroscopy Clinical Devices.
Several portable commercial bioimpedance spectroscopy (BIS) devices are used in clinical research, but are limited by their reduced impedance measuring range to less demanding four-electrode configuration measurements. Some of these devices provide raw bioimpedance data for research purposes. The SFB7 device from ImpediMed® is a typical portable clinical device which perform 256 measurement points from 3 kHz to 1 MHz, providing for each point the resistance R and the reactance X. Its main drawback is its impedance range, limited to only 1100 Ω, making it less suitable for more demanding, higher impedance, two-electrode measurements which are potentially of great clinical interest. Some benchtop reference devices have larger frequency and impedance ranges than the SFB7 but are not portable and are not designed specifically for BIS measurement on humans.This article proposes a method to overcome the impedance range limitation of the SFB7 by connecting in parallel to the investigated bioimpedance a fixed and known impedance, whose value (and hence that of the total measured impedance) is within the device's range. The investigated impedance is then calculated by eliminating the contribution of the known impedance via a post processing of the data.This concept has been successfully tested on a physical model, and an in vivo example has validated the practicality of performing demanding two-electrode measurements on individuals using a SFB7, with relative errors of R and X inferior to 2.5% and 7% respectively.Clinical Relevance- Using the proposed setup and after post processing of the data, the SFB7 BIS device can now be used to perform demanding two-electrode measurements, hitherto impossible, enabling a range of novel clinical, high-impedance studies, for example for localized skin characterization.


Effects of Odanacatib on Bone Structure and Quality in Postmenopausal Women With Osteoporosis: 5-Year Data From the Phase 3 Long-Term Odanacatib Fracture Trial (LOFT) and its Extension.
Odanacatib (ODN), a selective oral inhibitor of cathepsin K, was an investigational agent previously in development for the treatment of osteoporosis. In this analysis, the effects of ODN on bone remodeling/modeling and structure were examined in the randomized, double-blind, placebo-controlled, event-driven, Phase 3, Long-term Odanacatib Fracture Trial (LOFT; NCT00529373) and planned double-blind extension in postmenopausal women with osteoporosis. A total of 386 transilial bone biopsies, obtained from consenting patients at baseline (ODN n = 17, placebo n = 23), month 24 (ODN n = 112, placebo n = 104), month 36 (ODN n = 42, placebo n = 41), and month 60 (ODN n = 27, placebo n = 20) were assessed by dynamic and static bone histomorphometry. Patient characteristics at baseline and BMD changes over 5 years for this subset were comparable to the overall LOFT population. Qualitative assessment of biopsies revealed no abnormalities. Consistent with the mechanism of ODN, osteoclast number was higher with ODN versus placebo over time. Regarding bone remodeling, dynamic bone formation indices in trabecular, intracortical, and endocortical surfaces were generally similar in ODN-treated versus placebo-treated patients after 2 years of treatment. Regarding periosteal modeling, the proportion of patients with periosteal double labels and the bone formation indices increased over time in the ODN-treated patients compared with placebo. This finding supported the observed numerical increase in cortical thickness at month 60 versus placebo. In conclusion, ODN treatment for 5 years did not reduce bone remodeling and increased the proportion of patients with periosteal bone formation. These results are consistent with the mechanism of action of ODN, and are associated with continued BMD increases and reduced risk of fractures compared with placebo in the LOFT Phase 3 fracture trial. © 2020 American Society for Bone and Mineral Research.


Highly-Expressed MiR-221-3p Distinctly Increases the Incidence of Diabetic Retinopathy in Patients With Type 2 Diabetes Mellitus.
Diabetic retinopathy (DR) is the leading cause of blindness in patients with diabetes mellitus (DM). MiR-221-3p is implicated in microvascular dysfunction in DR, and we explored their relationship. Patients with type 2 diabetes mellitus (T2DM) were allocated to the non-DR (NDR)/nonproliferative DR (NPDR)/proliferative DR (PDR) groups, with their clinical baseline and pathological data collected. The miR-221-3p and VEGF levels were determined by reverse transcription quantitative polymerase chain reaction (RT-qPCR) and ELISA, respectively. Peripheral blood endothelial progenitor cell (EPC) and endothelial cell (EC) ratios were ascertained by flow cytometry. The correlations between miR-221-3p levels and VEGF/EPCs/ECs, the predictive value of serum miR-221-3p levels in DR, and the independent risk factors for DR occurrence in T2DM were analyzed by Pearson's correlation analysis, receiver operating characteristic (ROC) curve, and multifactorial logistic regression analysis. Serum miR-221-3p was highly expressed in DR. Clinical severity of DR was positively correlated with miR-221-3p levels. Endothelial function was impaired in DR. Serum miR-221-3p levels in DR were favorably correlated with VEGF and ECs and negatively associated with EPCs. The area under the curve of serum miR-221-3p in evaluating DR occurrence in patients with T2DM was 0.8178 (1.235 cutoff value, 69.62% sensitivity, and 82.35% specificity). High expression of miR-221-3p increased DR incidence in patients with T2DM. Diabetes course, VEGF, EPCs, ECs, and miR-221-3p levels were independent risk factors for DR development in patients with T2DM. Serum miR-221-3p levels in patients with DR were positively correlated with VEGF and ECs and negatively linked with EPCs. Highly expressed miR-221-3p distinctly increased DR incidence in patients with T2DM and was an independent risk factor for DR development in patients with T2DM. This study assessed serum miR-221-3p level and endothelial function indicators (VEGF, EPCs, and ECs) in patients with DR and analyzed the correlation between each indicator. We found that high serum miR-221-3p expression prominently increased the incidence of DR in patients with T2DM and was an independent risk factor for the development of DR in patients with T2DM. This study provided a scientific basis for further clarification of the pathogenesis of DR, and also provided new ideas for clinical prediction and management of DR.


Expression of Cloned Genes in Pichia pastoris Using the Methanol-Inducible Promoter AOX1.
Pichia pastoris is a methylotrophic yeast capable of metabolizing methanol as its sole carbon source. Growth in methanol-containing medium results in dramatic induction of genes in the alcohol oxidation pathway including alcohol oxidase (AOX), formaldehyde dehydrogenase (FLD), and dihydroxyacetone synthase (DHAS). These proteins may comprise up to 30% of the biomass. Investigators have exploited these methanol-dependent genes to generate tightly regulated expression vectors. Most Pichia vectors use the strong and tightly regulated AOX1 promoter to drive heterologous protein expression. Obtaining integrated Pichia transformants requires more DNA than transformations into Saccharomyces cerevisiae, where the gene is expressed from episomal plasmids; however, transformants are extremely stable and can be stored for many years.


2020, A Decisive Decade for NADPH Oxidases Inhibitors.
NADPH oxidases (Noxs) represent an original pharmacological target because they are the only enzymes whose main function is to produce reactive oxygen species. It is also a double target with the need for stimulation in chronic granulomatosis and inhibition reported in other pathologies (vascular, cancerous, neurological, etc.). The complexity of the involvement of Noxs in pathophysiology has not yet made it possible to obtain a drug that effectively inhibits these enzymes at the clinical level. This issue of the Forum aims to take stock of the obstacles and limitations to the development of these inhibitors both in their preclinical and clinical evaluation.


[Orientation illusions in weightlessness].
Results of the ANKETA and OPROSNIK experiments performed by 102 cosmonauts in and post flight were analysed. It is shown that perceptive disturbances (orientation illusions) developed in the period of early adaptation to weightlessness were not an inherent feature of individual persons but regular responses of the body sensory systems. The character, intensity, duration, and the dynamics of illusion responses in space mission are described. Forms of the vestibular disorders, types of adaptation of the sensory systems and classification of spontaneous illusion responses in the weightless environment are presented. Hypothesis for possible mechanisms of the illusion responses in weightlessness is suggested.


Transumbilical endoscopic surgery: History, present situation and perspectives.
Transumbilical endoscopic surgery or laparo-endoscopic single site (LESS) surgery has become an exciting area of surgical development as innovation continues to move in the 21(st) century to minimally invasive surgery. The history, present situation and perspectives are reviewed and the nomenclature of this technique is discussed in this article. The range of this technique has been applied in almost all abdominal diseases, surgeries for morbid obesity, hernia and so on, in recent years. It is estimated that 50%-80% of traditional laparoscopic surgery could be performed transumbilically in the next five years according to the LESSCAR consensus. Although the concept of transumbilical laparoscopic surgery is gaining traction rapidly and the instruments have been improved greatly, we should not advocate for slightly improved cosmetic value over safety. Multicenter, randomized and clinical trials are necessary to further elucidate the safety and efficiency of this new technique. Research that examines the efficacy of the new instruments on the market may be helpful to simplify the confusing landscape of new and novel products designed for this purpose.


Vascular pathology in Alzheimer's disease.
Histopathologically, numerous senile plaques and neurofibrillary tangles were remarkably observed in the brain with Alzheimer's disease. At the same time, so much simple atrophy of nerve cells was evident under light microscopy.Electron microscopical observations of serial sections revealed that small blood vessels, including capillaries, had a deep relationship to the amyloid fibrils which formed the senile plaques and they had fallen into degenerative states. The vascular feet of the astroglial cells surrounding small blood vessels showed degenerative features, and many nerve cells in this area either showed various degrees of degeneration or apparently were destroyed. The atrophy of the brain with Alzheimer's disease is considered to be caused by the amyloid angiopathy of small blood vessels and the degeneration of capillaries and vascular feet. These findings strongly suggest that the major causal mechanism of Alzheimer's disease is an alteration of the blood-brain barrier. Morphology is an expression of both the structure and the function of organs in the living body. Based on this viewpoint, this review article emphasizes that the morphological changes to small blood vessels in the brain with Alzheimer's disease convey crucial information and clues for solving the underlying mechanism that causes the disease.


An assessment of care provided by a public sector STD clinic in Cape Town.
A study was undertaken in a Cape Town public sector STD clinic to evaluate the content and quality of care provided since it has been recognized that appropriate improvements in the management of conventional sexually transmitted diseases (STDs), including provision of correct therapy, health education, condom promotion and partner notification, could result in a reduced incidence of HIV infection. Our objectives were to assess patients' needs for health education and to assess the quality of STD management in terms of health education, condom promotion, partner notification, the validity of the clinical diagnoses and the adequacy of the treatments prescribed. The study subjects were sampled systematically, according to their gender. Patients included in the study were given a standardized interview and their clinical records reviewed. Specimens were collected for laboratory investigations. For each STD detected, the treatment was defined as adequate if drugs currently known to be active against that infection were prescribed. One hundred and seventy men and 161 women were included in the study (median age: females 22 years, males 26 years). While almost all patients believed their STD may have been caused by unprotected sexual intercourse, many also believed it may have been caused by other factors, such as bewitchment with traditional medicine. Only 21% of male and 37% of female patients received any education about STD transmission during the clinic visit, and only 25% of male and 36% of female patients received education about condom use. As a result of the low sensitivity of the clinicians' diagnoses, 16% of men and 61% of women left the clinic with at least one infection inadequately treated. The majority of patients were not receiving education for the prevention of STDs including HIV. Many were not receiving adequate treatment for their infections. The introduction of a syndromic management protocol in this setting would substantially reduce the proportion of inadequately-treated patients. However, syndromic protocols, and the means by which they are implemented, need to take into account problems with the clinical detection of genital ulcerative disease and candidiasis in women.


[Computed tomography diagnosis of clinically well-tolerated bilateral lumbar vertebral synovial cysts].
We report two very rare cases of bilateral synovial cyst of the lumbar spine arising at the L4-L5 level. The diagnosis was made by CT without any ambiguity. The reported lesions illustrate almost the complete panel of CT findings in synovial cyst of the spine including gas formation, marginal calcifications, bone erosion of the adjacent lamina, and in one case the original development of an intracystic calcified nodule. The symptoms of the two patients improved with medical treatment only and spontaneous regression of the calcified cysts was confirmed in one case.


Development of a pHrodo-based assay for the assessment of in vitro and in vivo erythrophagocytosis during experimental trypanosomosis.
Extracellular trypanosomes can cause a wide range of diseases and pathological complications in a broad range of mammalian hosts. One common feature of trypanosomosis is the occurrence of anemia, caused by an imbalance between erythropoiesis and red blood cell clearance of aging erythrocytes. In murine models for T. brucei trypanosomosis, anemia is marked by a very sudden non-hemolytic loss of RBCs during the first-peak parasitemia control, followed by a short recovery phase and the subsequent gradual occurrence of an ever-increasing level of anemia. Using a newly developed quantitative pHrodo based in vitro erythrophagocytosis assay, combined with FACS-based ex vivo and in vivo results, we show that activated liver monocytic cells and neutrophils as well as activated splenic macrophages are the main cells involved in the occurrence of the early-stage acute anemia. In addition, we show that trypanosomosis itself leads to a rapid alteration of RBC membrane stability, priming the cells for accelerated phagocytosis.


Zinc transporter-8 autoantibodies can replace IA-2 autoantibodies as a serological marker for juvenile onset type 1 diabetes in India.
Zinc transporter-8 (ZnT8) is an islet cell secretory granule membrane protein recently identified as an autoantigen in type 1 diabetes (T1D). The aim of this study was to estimate the prevalence of antibodies to ZnT8 (ZnT8A) in juvenile onset T1D and to determine the utility of ZnT8A as an independent marker of autoimmunity either alone in antibody-negative subjects or in conjunction with glutamic acid decarboxylase (GAD) and insulinoma-2 antigen antibodies (GADA and IA2A). ZnT8A, GADA, and IA2A were measured in sera of consecutive T1D patients (n = 88, age range 2-18 years) within 4 years of diagnosis and 88 sex-matched controls. The prevalences of GADA, ZnT8a, and IA2A were 64.7%, 31.8% and 19.3%, respectively. In newly diagnosed patients, the frequency of ZnT8A was 45%. ZnT8A were positive in 26% of patients negative for both GADA and IA2A. IA2A were positive only in two patients who were negative for other two antibodies. Combined use of ZnT8A and GADA could detect 97% of antibody positive patients. In receiver operating characteristic (ROC) analysis, the performances of GADA and ZnT8As were better than that of IA2A; and AUCs of GADA, ZnT8A, and IA2A for the prediction of T1D were 0.8, 0.65, and 0.59, respectively. ZnT8A complements GADA and increases the diagnostic sensitivity for detection of autoimmunity in juvenile-onset T1D. Inclusion of ZnT8A increases the proportion of patients with antibody positivity to nearly 80%. ZnT8A can replace IA2A as a serological marker for autoimmunity in Indian T1D patients without loss of sensitivity and specificity.


Detection of c-kit mutations in canine mast cell tumors using fluorescent polyacrylamide gel electrophoresis.
Mutations consisting of internal tandem duplications (ITDs) in exons 11 and 12 of the proto-oncogene c-kit are found in 30-50% of malignant canine mast cell tumors (MCTs). Traditionally, identification of such mutations in tumor specimens has been undertaken using standard polymerase chain reaction (PCR) and agarose gel electrophoresis. This procedure is limited to the detection of insertions and deletions larger than 9 base pairs in size. The purpose of this study was to compare the efficiency and accuracy of standard agarose gel electrophoresis with fluorescent polyacrylamide gel electrophoresis (PAGE) for the detection of ITDs in canine MCTs. The results of this study demonstrate that PAGE of labeled PCR products accurately predicts the size of the ITD in each tumor. In addition, other small insertions and deletions were not identified, suggesting that if they occur in canine MCTs, they do so infrequently. Because fluorescent and polyacrylamide formats are automated and have better resolution than agarose gels, fluorescent PAGE provides a more accurate, economical, and higher throughput method for the detection of c-kit mutations in canine MCTs.


Iliac crest bone graft donor site pain after anterior lumbar interbody fusion: a prospective patient satisfaction outcome assessment.
Autogenous iliac crest bone is the gold-standard graft for spinal fusion surgery. Unfortunately, there is a frequent incidence of graft site pain that persists well into the postoperative period with complication rates reported in 2.8-39% of patients. Persistent pain lasting at least 2 years is reported in 15-39% of patients. The objective of this work was to determine the incidence of acute and persistent pain as well as patient assessment of graft site appearance following iliac crest bone graft harvest for anterior lumbar interbody fusion (ALIF). The control arms of four randomized prospective multicenter clinical trials evaluating recombinant human bone morphogenetic protein-2 (rhBMP-2) versus autogenous iliac crest bone graft were combined. Two hundred eight patients underwent iliac crest bone graft harvest for ALIF in threaded cylindrical cages or threaded bone dowels. Patients were assessed at each postoperative visit with questionnaires evaluating graft site pain intensity, duration, and appearance. Two hundred eight patients underwent iliac crest bone graft harvest for ALIF as the control group of four randomized prospective multicenter clinical trials evaluating rhBMP-2 versus autogenous iliac crest bone graft in threaded cylindrical cages or threaded bone dowels. Most patients in the control group had anterior iliac crest graft harvest, equally from the right and left side. Three grafts (1.4%) were taken from the posterior crest and six (2.9%) were tricortical. Follow-up was obtained at hospital discharge, 6 weeks, 3, 6, 12, and 24 months. A pain evaluation score was made up of two Visual Analog Scales: one scale measuring intensity, the other frequency of pain. For the intensity scale, a rating of "0" meant no pain and "10" was "as bad as it could be." For the frequency scale, a rating of "0" meant pain was present "none of the time" and "10" meant it was present "all the time." Combining these scales, a total score of 20 indicated the worst pain was present all the time. Patients were also questioned about the graft site appearance. Two hundred eight patients underwent iliac crest harvest, and prospective data were available on 202 patients. At hospital discharge, 2 patients (1%) had no pain; this increased to 34 of 199 (17%) at 6 weeks postoperatively and to 85 of 199 patients (43%) at 3 months. However, 41% of patients reported pain at 6 months postoperatively (79/192), and 33% of 168 reported pain at 1 year. One hundred forty-one of 208 patients completed a survey at 24 months, with 31% reporting some level of pain. At hospital discharge, the graft site pain score ranged from 0 to 20 with a mean of 12.8, decreasing to 7.3 at 6 weeks, to 3.8 at 3 months, and to 2.9, 2.4, and 1.8 at 6, 12, and 24 months, respectively. At all time intervals, P values from t tests comparing the mean with 0 were <0.001. Graft site appearance at discharge was good in 49% of patients, fair in 40%, and poor in 11%. At 6 weeks, appearance was good in 69%, fair in 27%, and poor in 5%; at 3 months, it was good in 75%, fair in 24%, and poor in 2%; at 6 months, it was good in 82%, fair in 15%, and poor in 3%; at 12 months, it was good in 82% and fair or poor in 19%; and at 24 months, it was good in 84% and fair or poor in 16%. There was no significant difference between posterior and anterior harvest sites or bicortical grafts, and all were included in the analysis. Right or left side demonstrated no differences. This is the first study known to the authors presenting results of prospective data collected in a multicenter study evaluating iliac crest harvest site pain, both intensity and frequency, as well as graft site appearance. The results demonstrate that 31% of patients had persistent pain at 24 months postoperatively and 16% reported fair or poor appearance of their graft site. Persistent donor site pain remains a problem with harvest of autogenous iliac crest bone graft for spinal fusion. This prospective study, the first such study reported for ALIF, confirms that donor site pain remains a significant postoperative management problem.


Recognition memory for emotional faces in amnestic mild cognitive impairment: an event-related potential study.
This study examined the temporal course of emotional face recognition in amnestic mild cognitive impairment (aMCI). Patients and healthy controls (HC) performed a face recognition task, giving old/new responses to previously studied and novel faces displaying a negative or neutral expression. In aMCI patients, recognition accuracy was preserved for negative faces. Event-related potentials (ERPs) revealed disease-related changes in early perceptual components but not in ERP indices of explicit recognition. Specifically, aMCI patients showed impaired recognition effects for negative faces on the amplitudes of N170 and P2, suggesting deficient memory-related processing of negative faces at the stage of structural encoding and during an early recognition stage at which faces are individuated, respectively. Moreover, while a right-lateralized emotion effect specifically observed for correctly recognized faces on the amplitude of N170 was absent in aMCI, a similar emotion effect for successfully recognized faces on P2 was preserved in the patients, albeit with a different distribution. This suggests that in aMCI facilitated processing of successfully recognized emotional faces starts later in the processing sequence. Nonetheless, an early frontal old/new effect confined to negative faces and a parietal old/new effect unaffected by facial emotion were observed in both groups. This indicates that familiarity and conceptual priming processes may specifically contribute to recognition of negative faces in older adults and that aMCI patients can recruit the same retrieval mechanisms as controls, despite disease-related changes on early perceptual ERP components.


PANCREATICODUODENECTOMY: IMPACT OF THE TECHNIQUE ON OPERATIVE OUTCOMES AND SURGICAL MORTALITY.
Pancreaticoduodenectomy (PD) is a procedure associated with significant morbidity and mortality. Initially described as gastropancreaticoduodenectomy (GPD), the possibility of preservation of the gastric antrum and pylorus was described in the 1970s. To evaluate the mortality and operative variables of PD with or without pyloric preservation and to correlate them with the adopted technique and surgical indication. Retrospective cohort on data analysis of medical records of individuals who underwent PD from 2012 through 2017. Demographic, anthropometric and operative variables were analyzed and correlated with the adopted technique (GPD vs. PD) and the surgical indication. Of the 87 individuals evaluated, 38 (43.7%) underwent GPD and 49 (53.3%) were submitted to PD. The frequency of GPD (62.5%) was significantly higher among patients with pancreatic neoplasia (p=0.04). The hospital stay was significantly shorter among the individuals submitted to resection due to neoplasias of less aggressive behavior (p=0.04). Surgical mortality was 10.3%, with no difference between GPD and PD. Mortality was significantly higher among individuals undergoing resection for chronic pancreatitis (p=0.001). There were no differences in mortality, surgical time, bleeding or hospitalization time between GPD and PD. Pancreas head neoplasm was associated with a higher indication of GPD. Resection of less aggressive neoplasms was associated with lower morbidity and mortality.


Effects of rainfall exclusion on leaf gas exchange traits and osmotic adjustment in mature canopy trees of Dryobalanops aromatica (Dipterocarpaceae) in a Malaysian tropical rain forest.
Climate change exposes vegetation to unusual levels of drought, risking a decline in productivity and an increase in mortality. It still remains unclear how trees and forests respond to such unusual drought, particularly Southeast Asian tropical rain forests. To understand leaf ecophysiological responses of tropical rain forest trees to soil drying, a rainfall exclusion experiment was conducted on mature canopy trees of Dryobalanops aromatica Gaertn.f. (Dipterocarpaceae) for 4 months in an aseasonal tropical rain forest in Sarawak, Malaysia. The rainfall was intercepted by using a soft vinyl chloride sheet. We compared the three control and three treatment trees with respect to leaf water use at the top of the crown, including stomatal conductance (gsmax), photosynthesis (Amax), leaf water potential (predawn: Ψpre; midday: Ψmid), leaf water potential at turgor loss point (πtlp), osmotic potential at full turgor (π100) and a bulk modulus of elasticity (ε). Measurements were taken using tree-tower and canopy-crane systems. During the experiment, the treatment trees suffered drought stress without evidence of canopy dieback in comparison with the control trees; e.g., Ψpre and Ψmid decreased with soil drying. Minimum values of Ψmid in the treatment trees decreased during the experiment, and were lower than πtlp in the control trees. However, the treatment trees also decreased their πtlp by osmotic adjustment, and the values were lower than the minimum values of their Ψmid. In addition, the treatment trees maintained gs and Amax especially in the morning, though at midday, values decreased to half those of the control trees. Decreasing leaf water potential by osmotic adjustment to maintain gs and Amax under soil drying in treatment trees was considered to represent anisohydric behavior. These results suggest that D. aromatica may have high leaf adaptability to drought by regulating leaf water consumption and maintaining turgor pressure to improve its leaf water relations.


Assessment of EVAR Complications using CIRSE Complication Classification System in the UK Tertiary Referral Centre: A ∼6-Year Retrospective Analysis (2014-2019).
To retrospectively analyse complications in endovascular aortic repair (EVAR) interventions and evaluate if the CIRSE (Cardiovascular and Interventional Radiological Society of Europe) complication classification system is appropriate as a standardized classification tool for EVAR patients. Demographic, procedural and complication data in 719 consecutive patients undergoing EVAR at one institution from January 2014 to October 2019 were retrospectively reviewed. Data (imaging reports, procedural reports, nurse notes, discharge summary reports) were collected consulting the electronic patient record system (EPR) of the hospital and cleaned and stored in a Microsoft Excel database. All the procedures were analysed in consensus by two interventional radiology consultants and a resident radiologist and if an intra- , peri- or post-procedural complication occurred, a grade (1-6) was assigned using the CIRSE grading complication classification system. Twenty-five patients were excluded from the analysis because of invalid or incomplete data. The final population was made up of 694 patients (mean age 75,4 y.o., 616 male/78 female, min age 23 y.o., max age 97 y.o.). Complications emerged in 211 patients (30,4% of cases, 22 female/189 male). The number of patients with CIRSE grade I, II, III, IV, V and VI complications was 36 (17%), 17 (8%), 121 (57,3%), 15 (7,1%), 3 (1,4%), 19 (9%). Nineteen (2,6%) patients succumbed after EVAR. Thirty-four complications (16,1%) were related to vascular access. The CIRSE complication classification system represents a broadly applicable and feasible approach to evaluate the severity of complications in patients following EVAR. However, some deficit may be considered relevant and as starting standing-point for future improvements.


Behavioral problems in school-aged hearing-impaired children: the influence of sociodemographic, linguistic, and medical factors.
The purpose of this study was to examine several behavioral problems in school-aged hearing-impaired children with hearing aids or cochlear implants, compared to normally hearing children. Additionally, we wanted to investigate which sociodemographic, linguistic, and medical factors contributed to the level of behavioral problems, to pinpoint where targeted interventions can take place. This large, retrospective study included a sample of 261 school-aged children (mean age = 11.8 years, SD = 1.6), that consisted of three age- and gender-matched subgroups: 75 with hearing aids, 57 with cochlear implants, and 129 normally hearing controls. Self- and parent-reports concerning reactive and proactive aggression, delinquency, and symptoms of psychopathy, attention deficit hyperactivity disorder, oppositional defiant disorder, and conduct disorder were used. In addition, several language and intelligence tests were administered. Hearing-impaired children showed significantly more proactive aggression, symptoms of psychopathy, attention deficit hyperactivity disorder, oppositional defiant disorder, and conduct disorder than their normally hearing peers. More behavioral problems were associated with special schools for the deaf, sign (-supported) language, hearing aids (in contrast to cochlear implants), higher age, male gender, lower socioeconomic status, lower intelligence, and delayed language development. Hearing-impaired children face multiple problems regarding their behavior. The outcomes implicate that professionals should be aware of the higher risk of developing behavioral problems, in order to screen, detect, and treat in time. Furthermore, the associated risk and protective factors emphasize that clinicians must always consider the heterogeneity of the group of hearing-impaired children, in order to help and support the individual patient.


Tryptophan contaminants associated with eosinophilia-myalgia syndrome. The Eosinophilia-Myalgia Studies of Oregon, New York and New Mexico.
Eosinophilia-myalgia syndrome (EMS) has been linked to ingestion of tryptophan contaminated with 1,1'-ethylidene-bis[L-tryptophan] (EBT), but other contaminants have received little study. The authors identified 101 lots of L-tryptophan that had been consumed either by persons with EMS or by asymptomatic tryptophan users and quantified the amounts of EBT and five other contaminants in each lot. After stratification of case and noncase lots by time of manufacture to adjust for the strong sequential pattern over time among case and noncase lots, higher EBT levels were still associated with a lot's case status, but the association lacked statistical significance (p = 0.120, odds ratio = 1.56, 95% confidence interval 0.758-3.23). While these findings do not rule out the possibility that EBT is the etiologic agent in EMS, they raise the possibility that other chemical contaminants in manufactured tryptophan modify the effects of EBT or that the causal agent of EMS is an entirely distinct compound.


Is the course of brain development in schizophrenia delayed? Evidence from onsets in adolescence.
A degree of ventricular enlargement, together with a reduction of total cortical mass and loss of asymmetry is reported in schizophrenia, but the meaning is obscure. These changes may reflect an anomaly of brain development. Brain structure was assessed on a 1.5-Tesla MRI scan in a series of 29 adolescents at the time of a first episode of schizophrenia and compared with 15 adolescents with other serious psychiatric disturbance (mostly psychotic) and 20 normal adolescent controls. The age at scan ranged between 13 and 20 years. In the adolescents with a diagnosis of schizophrenia, total brain volume increased with age in a way that differed significantly (p=0.007) from that seen in patients with other psychiatric disturbance and normal controls. Thus, brain growth, as assessed by this index, had reached a plateau in the control group by the age of 13 years, but this was not true of patients with schizophrenia. The measure that most clearly distinguished the groups (p<0.001 after co-varying for height and sex) was the volume of the left lateral ventricle the ventricle was significantly larger in patients with schizophrenic illness, and ventricular size increased with age to a greater extent in the patient group, although not significantly so, than in normal controls. Thus, aspects of brain growth are delayed in patients with early onset schizophrenia, and the greatest severity of illness is reflected in a component of growth that is lateralized to the dominant hemisphere. Individuals who develop serious psychiatric illness, including schizophrenia, represent a fraction of the population in whom a component of the relative development of the cerebral hemispheres occurs late.


Basing perceptual decisions on the most informative sensory neurons.
Single unit recording studies show that perceptual decisions are often based on the output of sensory neurons that are maximally responsive (or "tuned") to relevant stimulus features. However, when performing a difficult discrimination between two highly similar stimuli, perceptual decisions should instead be based on the activity of neurons tuned away from the relevant feature (off-channel neurons) as these neurons undergo a larger firing rate change and are thus more informative. To test this hypothesis, we measured feature-selective responses in human primary visual cortex (V1) using functional magnetic resonance imaging and show that the degree of off-channel activation predicts performance on a difficult visual discrimination task. Moreover, this predictive relationship between off-channel activation and perceptual acuity is not simply the result of extensive practice with a specific stimulus feature (as in studies of perceptual learning). Instead, relying on the output of the most informative sensory neurons may represent a general, and optimal, strategy for efficiently computing perceptual decisions.


Subgenome dominance shapes novel gene evolution in the decaploid pitcher plant Nepenthes gracilis.
Subgenome dominance after whole-genome duplication generates distinction in gene number and expression at the level of chromosome sets, but it remains unclear how this process may be involved in evolutionary novelty. Here we generated a chromosome-scale genome assembly of the Asian pitcher plant Nepenthes gracilis to analyse how its novel traits (dioecy and carnivorous pitcher leaves) are linked to genomic evolution. We found a decaploid karyotype and a clear indication of subgenome dominance. A male-linked and pericentromerically located region on the putative sex chromosome was identified in a recessive subgenome and was found to harbour three transcription factors involved in flower and pollen development, including a likely neofunctionalized LEAFY duplicate. Transcriptomic and syntenic analyses of carnivory-related genes suggested that the paleopolyploidization events seeded genes that subsequently formed tandem clusters in recessive subgenomes with specific expression in the digestive zone of the pitcher, where specialized cells digest prey and absorb derived nutrients. A genome-scale analysis suggested that subgenome dominance likely contributed to evolutionary innovation by permitting recessive subgenomes to diversify functions of novel tissue-specific duplicates. Our results provide insight into how polyploidy can give rise to novel traits in divergent and successful high-ploidy lineages.


Single-nucleotide polymorphism of the DNA cytosine deaminase APOBEC3H haplotype I leads to enzyme destabilization and correlates with lung cancer.
A number of APOBEC family DNA cytosine deaminases can induce mutations in tumor cells. APOBEC3H haplotype I is one of the deaminases that has been proposed to cause mutations in lung cancer. Here, we confirmed that APOBEC3H haplotype I can cause uracil-induced DNA damage in lung cancer cells that results in γH2AX foci. Interestingly, the database of cancer biomarkers in DNA repair genes (DNArCdb) identified a single-nucleotide polymorphism (rs139298) of APOBEC3H haplotype I that is involved in lung cancer. While we thought this may increase the activity of APOBEC3H haplotype I, instead we found through computational modeling and cell-based experiments that this single-nucleotide polymorphism causes the destabilization of APOBEC3H Haplotype I. Computational analysis suggests that the resulting K121E change affects the structure of APOBEC3H leading to active site disruption and destabilization of the RNA-mediated dimer interface. A K117E mutation in a K121E background stabilized the APOBEC3H haplotype I, thus enabling biochemical study. Subsequent analysis showed that K121E affected catalytic activity, single-stranded DNA binding and oligomerization on single-stranded DNA. The destabilization of a DNA mutator associated with lung cancer supports the model that too much APOBEC3-induced mutation could result in immune recognition or death of tumor cells.


Patients' Perceptions of Short-Term Recovery After a Gastric Bypass.
To explore gastric bypass patients' perceptions of their postoperative recovery over 1 month. A standardized questionnaire, the postoperative recovery profile, was used. Postoperative recovery profile is a multi-item questionnaire for self-assessment of general postoperative recovery. Participants were patients who had undergone gastric bypass surgery (n = 39). The changes in recovery between 1 day and 1 month postsurgery were evaluated by a statistical method developed specifically for analyzing changes in paired ordered data over time. Most of the symptoms and/or functions were significantly improved on a group level. The most marked improvement was to pain and sleeping difficulties followed by mobilization. In terms of the psychological items, the proportion of patients who indicated no problems was high at both endpoints. The items that deviated from the improvement pattern were appetite changes and gastrointestinal function which demonstrated a relatively high proportion of deterioration, and the individual variability was prominent. There is a need for interventions to improve recovery on a group as well as an individual level.


Amaranthus hybridus (syn. quitensis) intoxication in cattle in Argentina: Case report.
Amaranthus spp. is a nephrotoxic plant with unknown toxic principle, affecting production animals worldwide, mainly in South America. The aim of this paper is to describe 5 spontaneous outbreaks of A. hybridus intoxication in beef cattle, where 7 autopsies were performed. Main gross findings were pale diffuse and enlarged kidneys. Microscopically, kidneys were characterized by severe tubular acute to subacute nephrosis, with dilatated tubules showing different degrees of epithelial degeneration and necrosis, and containing intraluminal eosinophilic hyaline casts. Intratubular birefringent crystals, compatible with oxalate, were observed under polarized light in kidneys from 3 autopsies. Positive von Kossa and red alizarin S staining confirmed the intratubular crystals as calcium deposits. This intoxication occurs mainly in stubble paddocks during summer and early autumn. The data from the present study suggests that oxalates were related to nephrotoxicity due to Amaranthus consumption.


Anticoagulation therapy in children.
Thromboembolic disease (TED) is increasingly recognized as a major cause of morbidity and mortality in tertiary pediatrics. Children younger than 1 year of age and teenage girls are at greatest risk of thromboembolism. Although anticoagulation therapy is the treatment of choice for TED, the treatment strategy is often difficult, especially in children. Treatment relies largely on anticoagulation with heparin and warfarin. Recommendations for antithrombotic therapy in children have been loosely extrapolated from recommendations for adults; however, it is likely that optimal treatment of children with TED differs from adults because of important ontogenic features of hemostasis that affect both the pathophysiology of the thrombotic processes and the response to antithrombotic agents. Until recently, the primary treatment for TED has been unfractionated heparin (UFH) in conjunction with warfarin. Warfarin, the most commonly used oral anticoagulant, acts through inhibition of the vitamin K-dependent transcarboxylation reactions that convert precursors of clotting factors into their active form. Appropriate use of UFH and warfarin requires close patient monitoring and dosage adjustments to ensure tolerability and efficacy. In recent years, low molecular weight heparins (LMWH) have become available as alternatives to UFH and warfarin, for both the prevention and treatment of TED. Potentially, LMWH have significant advantages. They have superior pharmacokinetics, which results in minimal laboratory monitoring, offering important benefits to children with poor venous access. Based on available data, LMWHs are at least as effective and well tolerated as UFH, and are more convenient. Although LMWHs are more expensive than UFH, the expense is likely to be offset by savings from a reduced hospital stay.


Progress towards the discovery of orally active thrombin inhibitors.
The serine protease thrombin is a key enzyme in the control of blood coagulation and displays numerous other effects on platelet, endothelial and smooth muscle cell function. The pre-eminence of thrombin in the coagulation cascade has made the enzyme a popular drug target in the search for more clinically acceptable and safe anti-coagulants. This concept has been particularly strengthened by the demonstration that direct inhibitors of thrombin such as Revasc are clinically effective. A number of low molecular weight thrombin inhibitors have now been described in the literature although to date because of their inherent low bioavailability compounds have been limited to the parenteral route of administration. The introduction of appropriate pharmacokinetic properties into these first generation thrombin inhibitors has been problematic despite intensive research in this area. However, the first pre clinical examples of direct thrombin inhibitors possessing good oral bioavailability is now emerging. This review updates current developments in the progress towards the discovery of orally available thrombin inhibitors and suggests that the first clinical validation of drugs from this field is imminent.


Tissue-specific, tumor-selective, replication-competent adenovirus vector for cancer gene therapy.
We have previously described two replication-competent adenovirus vectors, named KD1 and KD3, for potential use in cancer gene therapy. KD1 and KD3 have two small deletions in the E1A gene that restrict efficient replication of these vectors to human cancer cell lines. These vectors also have increased capacity to lyse cells and spread from cell to cell because they overexpress the adenovirus death protein, an adenovirus protein required for efficient cell lysis and release of adenovirus from the cell. We now describe a new vector, named KD1-SPB, which is the KD1 vector with the E4 promoter replaced by the promoter for surfactant protein B (SPB). SPB promoter activity is restricted in the adult to type II alveolar epithelial cells and bronchial epithelial cells. Because KD1-SPB has the E1A mutations, it should replicate within and destroy only alveolar and bronchial cancer cells. We show that KD1-SPB replicates, lyses cells, and spreads from cell to cell as well as does KD1 in H441 cells, a human cancer cell line where the SPB promoter is active. KD1-SPB replicates, lyses cells, and spreads only poorly in Hep3B liver cancer cells. Replication was determined by expression of the E4ORF3 protein, viral DNA accumulation, fiber synthesis, and virus yield. Cell lysis and vector spread were measured by lactate dehydrogenase release and a "vector spread" assay. In addition to Hep3B cells, KD1-SPB also did not express E4ORF3 in HT29.14S (colon), HeLa (cervix), KB (nasopharynx), or LNCaP (prostate) cancer cell lines, in which the SPB promoter is not expected to be active. Following injection into H441 or Hep3B tumors growing in nude mice, KD1-SPB caused a three- to fourfold suppression of growth of H441 tumors, similar to that seen with KD1. KD1-SPB had only a minimal effect on the growth of Hep3B tumors, whereas KD1 again caused a three- to fourfold suppression. These results establish that the adenovirus E4 promoter can be replaced by a tissue-specific promoter in a replication-competent vector. The vector has three engineered safety features: the tissue-specific promoter, the mutations in E1A that preclude efficient replication in nondividing cells, and a deletion of the E3 genes which shield the virus from attack by the immune system. KD1-SPB may have use in treating human lung cancers in which the SPB promoter is active.


Geobacillus and Bacillus Spore Inactivation by Low Energy Electron Beam Technology: Resistance and Influencing Factors.
Low energy electron beam (LEEB) treatment is an emerging non-thermal technology that performs surface decontamination with a minimal influence on food quality. Bacterial spore resistance toward LEEB treatment and its influencing factors were investigated in this study. Spores from Geobacillus and Bacillus species were treated with a lab-scale LEEB at energy levels of 80 and 200 keV. The spore resistances were expressed as D-values (the radiation dose required for one log10 reduction at a given energy level) calculated from the linear regression of log10 reduction against absorbed dose of the sample. The results revealed that the spore inactivation efficiency by LEEB is comparable to that of other ionizing radiations and that the inactivation curves are mostly log10-linear at the investigated dose range (3.8 - 8.2 kGy at 80 keV; 6.0 - 9.8 kGy at 200 keV). The D-values obtained from the wildtype strains varied from 2.2 - 3.0 kGy at 80 keV, and from 2.2 - 3.1 kGy at 200 keV. Bacillus subtilis mutant spores lacking α/β-type small, acid-soluble spore proteins showed decreased D-values (1.3 kGy at 80 and 200 keV), indicating that spore DNA is one of the targets for LEEB spore inactivation. The results revealed that bacterial species, sporulation conditions and the treatment dose influence the spore LEEB inactivation. This finding indicates that for the application of this emerging technology, special attention should be paid to the choice of biological indicator, physiological state of the indicator and the processing settings. High spore inactivation efficiency supports the application of LEEB for the purpose of food surface decontamination. With its environmental, logistical, and economic advantages, LEEB can be a relevant technology for surface decontamination to deliver safe, minimally processed and additive-free food products.


Expression of water-soluble nucleocapsid protein of SARS-CoV-2 and analysis of its immunogenicity.
Coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) continues to be a major public health concern. Nucleocapsid (N) protein is the most abundant structural protein on SARS-CoV-2 virions and induces the production of antibodies at the early stage of infection. Large-scale preparation of N protein is essential for the development of immunoassays to detect antibodies to SARS-CoV-2 and the control of virus transmission. In this study, expression of water-soluble N protein was achieved through inducing protein expression at 25°C with 0.5 mM IPTG for 12 h. Western blot and ELISA showed that recombinant N protein could be recognized by sera collected from subjects immunized with Sinovac inactivated SARS-CoV-2 vaccine. Four monoclonal antibodies namely 2B1B1, 4D3A3, 5G1F8, and 7C6F5 were produced using hybridoma technology. Titers of all four monoclonal antibodies in ELISA reached more than 1.28×10 6.0. Moreover, all monoclonal antibodies could react specifically with N protein expressed by transfection of pcDNA3.1-N into BHK-21 cells in IPMA and IFA. These results indicated that water-soluble N protein retained high immunogenicity and possessed the same epitopes as that of native N protein on virions. In addition, the preparation of water-soluble N protein and its monoclonal antibodies laid the basis for the development of immunoassays for COVID-19 detection.


[Pre-hospital resuscitation and transport of cardiac patients. Apropos of 107 cases of primary transport].
Report of 107 cases of primary transportation in ambulances especially equipped for coronary patients monitoring. The various delays of admission were studied and the complications occuring during transportation were analyzed, together with the various therapeutic methods applied. On the basis of this personal experience, and to attempt at diminishing the mortality at the acute stage of myocardial infarction, it was advised: --a careful information of the public, --a systematic training of the physicians, --a logic organization of emergency care. Only a coherent set up of fixed and mobile units might result in improvement of the prognosis of the first hours after myocardial infarction.


Diagnosis and management of hepatocellular carcinoma: results of a consensus meeting of The Ottawa Hospital Cancer Centre.
Hepatocellular carcinoma (HCC) is an uncommon tumour, but its incidence is increasing in Canada and elsewhere. Currently, there are no Canadian recommendations for diagnosis and treatment of hcc, and possible options may have regional limitations. A consensus symposium was held in the Ottawa region to consider current diagnostic and management options for hcc. These recommendations were developed: Diagnosis-with adequate imaging, a biopsy is not required pre-surgery, but is required before the start of systemic therapy; lesions smaller than 1 cm should be followed and not biopsied; repeat biopsies should be core tissue biopsies; magnetic resonance imaging is preferred, but triphasic computed tomography imaging can be useful. Resection-recommended for localized HCC. Radiofrequency ablation-recommended for unresectable or non-transplantable HCC; should not be performed in the presence of ascites. Trans-arterial chemoembolization (TACE)-doxorubicin with lipiodol is the agent of choice; trans-catheter embolization is an alternative for patients if TACE is not tolerated or is contraindicated. Medical management-first-line sorafenib should be considered the standard of care. Transplantation-suitable patients meeting Milan criteria should be assessed for a graft regardless of other treatments offered. The authors feel that the recommendations from this consensus symposium may be of interest to other regions in Canada.


[Antioxidants and oxidative stress].
Oxidative damage is related to the development of several diseases. An improved antioxidant defence may therefore protect against these diseases. Recent studies have demonstrated that dietary plants contain several hundred different antioxidants. We have systematically assessed the total amount of antioxidants in a variety of dietary plants by the "ferric-reducing ability of plasma" assay, a method that measures the sum total of all antioxidants above a reference redox potential. Our results demonstrate that antioxidant levels vary considerably. Plants with the highest values include dog rose, sour cherry, blackberry, crowberry, blueberry, walnuts, sunflower seed, pomegranate and ginger. Among the dried culinary herbs tested, we found very high levels of antioxidants in oregano, sage, peppermint, garden thyme, lemon balm, clove, allspice and cinnamon. Our results are in accordance with studies in experimental animals demonstrating beneficial effect against age-related neurodegeneration, carcinogenesis and atherosclerosis after treatment with some of the most antioxidant-rich foods identified in the present study.


A Rare Case of Pseudo-Malignant Paranasal Extranodal Rosai-Dorfman Disease.
Rosai-Dorfman disease is a very rare disease characterized by histiocytic accumulation in the head and neck region and lymph node enlargement. We report a rare pseudo-malignant paranasal extranodal Rosai-Dorfman disease. A 69-year-old-man presented nasal bleeding and nasal obstruction. Paranasal mass was detected in the left nasal cavity and computed tomography (CT) findings are the sphenoid sinus, maxillary sinus, and ethmoid sinus were involved with inconstant bone thickening, however, no bone destruction was detected. Magnetic resonance imaging scans show iso-intensity signal in T1-weighed image and T2-weighed image. Positron emission tomography/CT fluorodeoxyglucose (FDG) uptake in posterior ethmoid sinus and sphenoid sinus, bilateral cervical lymph node, clavicle, and sternum. Based on the above results, we considered malignant lymphoma and performed a biopsy. After pathological examination, a diagnosis of Rosai-Dorfman disease was established.


A four-step approach for establishment of a national medical response to mega-terrorism.
A simplified, four-step approach was used to establish a medical management and response plan to mega-terrorism in Israel. The basic steps of this approach are: (1) analysis of a scenario based on past incidents; (2) description of relevant capabilities of the medical system; (3) analysis of gaps between the scenario and the expected response; and (4) development of an operational framework. Analyses of both the scenario and medical abilities led to the recommendation of an evidence-based contingency plan for mega-terrorism. An important lesson learned from the analyses is that a shortage in medical first responders would require the administration of advanced life support (ALS) by paramedics at the scene, along with simultaneous, rapid evacuation of urgent casualties to nearby hospitals by medics practicing basic life support (BLS). Ambulances and helicopters should triage casualties from inner to outer circle hospitals secondarily, preferentially Level-1 trauma centers. In conclusion, this four-step approach based on scenario analysis, mapping of medical capabilities, detection of bottlenecks, and establishment of a unique operational framework, can help other medical systems develop a response plan to mega-terrorist attacks.


Mechanical bound states in the continuum for macroscopic optomechanics.
Bound states in the continuum (BICs), an emerging type of long-lived resonances different from the cavity-based ones, have been explored in several classical systems, including photonic crystals and surface acoustic waves. Here, we reveal symmetry-protected mechanical BICs in the structure of slab-on-substrate optomechanical crystals. Using a group theory approach, we identified all the mechanical BICs at the Γ point in optomechanical crystals with C4v and C6v symmetries as examples, and analyzed their coupling with the co-localized optical BICs and guided resonances due to both moving boundary and photo-elastic effects. We verified the theoretical analysis with numerical simulations of specific optomechanical crystals which support substantial optomechanical interactions between the mechanical BICs and optical resonances. Due to the unique features of high-Q, large-size mechanical BICs and substrate-enabled thermal dissipation, this architecture of slab-on-substrate optomechanical crystals might be useful for exploring macroscopic quantum mechanical physics and enabling new applications such as high-throughput sensing and free-space beam steering.


Interventions to reduce medication errors in pediatric intensive care.
To systematically examine the research literature to identify which interventions reduce medication errors in pediatric intensive care units. Databases were searched from inception to April 2014. Studies were included if they involved the conduct of an intervention with the intent of reducing medication errors. In all, 34 relevant articles were identified. Apart from 1 study, all involved single-arm, before-and-after designs without a comparative, concurrent control group. A total of 6 types of interventions were utilized: computerized physician order entry (CPOE), intravenous systems (ISs), modes of education (MEs), protocols and guidelines (PGs), pharmacist involvement (PI), and support systems for clinical decision making (SSCDs). Statistically significant reductions in medication errors were achieved in 7/8 studies for CPOE, 2/5 studies for ISs, 9/11 studies for MEs, 1/2 studies for PGs, 2/3 studies for PI, and 3/5 studies for SSCDs. The test for subgroup differences showed that there was no statistically significant difference among the 6 subgroups of interventions, χ(2)(5) = 1.88, P = 0.87. The following risk ratio results for meta-analysis were obtained: CPOE: 0.47 (95% CI = 0.28, 0.79); IS: 0.37 (95% CI = 0.19, 0.73); ME: 0.36 (95% CI = 0.22, 0.58); PG: 0.82 (95% CI = 0.21, 3.25); PI: 0.39 (95% CI = 0.10, 1.51), and SSCD: 0.49 (95% CI = 0.23, 1.03). Available evidence suggests some aspects of CPOE with decision support, ME, and IS may help in reducing medication errors. Good quality, prospective, observational studies are needed for institutions to determine the most effective interventions.


Manganese Dioxide-Entrapping Dendrimers Co-Deliver Protein and Nucleotide for Magnetic Resonance Imaging-Guided Chemodynamic/Starvation/Immune Therapy of Tumors.
Development of a nanoscale drug delivery system that can simultaneously exert efficient tumor therapeutic efficacy while creating the desired antitumor immune responses is still challenging. Herein, we report the use of a manganese dioxide (MnO2)-entrapping dendrimer nanocarrier to codeliver glucose oxidase (GOx) and cyclic GMP-AMP (cGAMP), an agonist of the stimulator of interferon genes (STING) for improved tumor chemodynamic/starvation/immune therapy. Methoxy poly(ethylene glycol) (mPEG)- and phenylboronic acid (PBA)-modified generation 5 (G5) poly(amidoamine) dendrimers were first synthesized and then entrapped with MnO2 nanoparticles (NPs) to generate the hybrid MnO2@G5-mPEG-PBA (MGPP) NPs. The created MGPP NPs with an MnO2 core size of 2.8 nm display efficient glutathione depletion ability, and a favorable Mn2+ release profile under a tumor microenvironment mimetic condition to enable Fenton-like reaction and T1-weighted magnetic resonance (MR) imaging. We show that the MGPP-mediated GOx delivery facilitates enhanced chemodynamic/starvation therapy of cancer cells in vitro, and further codelivery of cGAMP can effectively trigger immunogenic cell death (ICD) to strongly promote the maturation of dendritic cells. In a bilateral mouse colorectal tumor model, the dendrimer delivery nanosystem elicits a potent antitumor performance with a strong abscopal effect, greatly improving the overall mouse survival rate. Importantly, the dendrimer-mediated codelivery not only allows the coordination of Mn2+ with GOx and cGAMP for respective chemodynamic/starvation-triggered ICD and augmented STING activation to boost systemic antitumor immune responses, but also enables T1-weighted tumor MR imaging, potentially serving as a promising nanoplatform for enhanced antitumor therapy with desired immune responses.


Environmental assessment of three egg production systems--Part I: Monitoring system and indoor air quality.
To comprehensively assess conventional vs. some alternative laying-hen housing systems under U.S. production conditions, a multi-institute and multi-disciplinary project, known as the Coalition for Sustainable Egg Supply (CSES) study, was carried out at a commercial egg production farm in the Midwestern United States over two single-cycle production flocks. The housing systems studied include a conventional cage house (200,000 hen capacity), an aviary house (50,000 hen capacity), and an enriched colony house (50,000 hen capacity). As an integral part of the CSES project, continual environmental monitoring over a 27-month period described in this paper quantifies indoor gaseous and particulate matter concentrations, thermal environment, and building ventilation rate of each house. Results showed that similar indoor thermal environments in all three houses were maintained through ventilation management and environmental control. Gaseous and particulate matter concentrations of the enriched colony house were comparable with those of the conventional cage house. In comparison, the aviary house had poorer indoor air quality, especially in wintertime, resulting from the presence of floor litter (higher ammonia levels) and hens' activities (higher particulate matter levels) in it. Specifically, daily mean indoor ammonia concentrations had the 95% confidence interval values of 3.8 to 4.2 (overall mean of 4.0) ppm for the conventional cage house; 6.2 to 7.2 (overall mean of 6.7) ppm for the aviary house; and 2.7 to 3.0 (overall mean of 2.8) ppm for the enriched colony house. The 95% confidence interval (overall mean) values of daily mean indoor carbon dioxide concentrations were 1997 to 2170 (2083) ppm for the conventional cage house, 2367 to 2582 (2475) ppm for the aviary house, and 2124 to 2309 (2216) ppm for the enriched colony house. Daily mean indoor methane concentrations were similar for all three houses, with 95% confidence interval values of 11.1 to 11.9 (overall mean of 11.5) ppm. The 95% confidence interval values (overall mean) of daily mean PM10 and PM2.5 concentrations, in mg/m3, were, respectively, 0.57 to 0.61 (0.59) and 0.033 to 0.037 (0.035) for the conventional cage house, 3.61 to 4.29 (3.95) and 0.374 to 0.446 (0.410) for the aviary house, and 0.42 to 0.46 (0.44) and 0.054 to 0.059 (0.056) for the enriched colony house. Investigation of mitigation practices to improve indoor air quality of the litter-floor aviary housing system is warranted.


Adsorption of molecular hydrogen on coronene with a new potential energy surface.
Benchmark interaction energies between coronene, C24H12, and molecular hydrogen, H2, have been computed by means of high level electronic structure calculations. Binding energies, equilibrium distances and strengths of the long range attraction, evaluated for the basic configurations of the H2-C24H12 complex, indicate that the system is not too affected by the relative orientations of the diatom, suggesting that its behavior can be approximated to that of a pseudoatom. The obtained energy profiles have confirmed the noncovalent nature of the bonding and serve to tune-up the parameters of a new force field based on the atom-bond approach which correctly describes the main features of the H2-coronene interaction. The structure and binding energies of (para-H2)N-coronene clusters have been investigated with an additive model for the above mentioned interactions and exploiting basin-hopping and path integral Monte Carlo calculations for N = 1-16 at T = 2 K. Differences with respect to the prototypical (rare gas)N-coronene aggregates have been discussed.


N,N-Dimethylation of nitrobenzenes with CO2 and water by electrocatalysis.
We have proposed a strategy for the synthesis of N,N-dimethylanilines from nitrobenzene and its derivatives, CO2, and water via an electrochemical reaction under ambient conditions. H+ generated from H2O was used as the hydrogen source. Pd/Co-N/carbon, in which the Pd nanoparticles were supported on Co-N/carbon, was designed and used as the electrocatalyst. It was found that the electrocatalyst was very efficient for the reaction in MeCN solution with 1-butyl-3-methylimidazolium bis(trifluoromethylsulfonyl)imide ([Bmim]Tf2N) as the supporting electrolyte and 1-amino-methylphosphonic acid (AMPA) as the thermal co-catalyst. A series of control experiments showed that Pd/Co-N/carbon and AMPA cooperated very well in accelerating the reaction. This synthetic route has some obvious advantages, such as using CO2 and water as the reactants, ambient reaction conditions, and high yields of the desired products. This opens up a way to synthesize chemicals by the combination of an electrocatalyst and a thermal catalyst with organic compounds, CO2, and water as the reactants.


Role of CCL2/MCP-1 in islet transplantation.
High levels of donor-derived CCL2 have been associated with poor islet allograft outcome in patients with type 1 diabetes. The aim of our work was to determine whether CCL2 secreted by the islet has independent proinflammatory effects that influence engraftment and graft acceptance. Both in mice and humans CCL2 is significantly positively associated with other cytokines/chemokines, in particular with the highly released "proinflammatory" IL-6 and CXCL8 or CXCL1. Transplantation of CCL2-/- islets into syngenic recipients did not improve the transplant function. Transplantation of islets into CCL2-/- syngenic recipients led to a significant improvement of transplant function and partial abrogation of local hepatic inflammation. When evaluated in human islets CCL2 release was strongly related to the immediate local inflammatory response in the liver and impacted short-term human islet function dependently by the induced inflammatory response and independently by the immunosuppressive therapy. The data showed that islet CCL2 release is a sign of "inflamed" islets without having a direct role in graft failure. On the other hand, a causal effect for developing detrimental proinflammatory conditions after transplant was proved for recipient CCL2. Strategies to selectively decrease recipient, but not donor, CCL2 release may increase the success of islet transplantation.


Effects of beta-carbolines of plasma corticosterone in mice.
6-Methoxy-1, 2, 3, 4-tetrahydro-beta-carboline, a drug which has been reported to increase brain serotonin (5-HT) but not norepinephrine, was tested for its acute effects of pituitary-adrenocortical activity in CF1 mice. The drug produced dose- and time-dependent increases in plasma corticosterone concentration which could be prevented by blocking adrenocorticotropic hormone secretion. Administration of other beta-carbolines or the 5-HT precursor 5-hydroxytryptophan also resulted in plasma corticosterone elevations. Further studies will be needed to determine whether beta-carbolines stimulate pituitary-adrenocortical activity through a central serotonergic system or by some alternate mechanism.


Current Trends and Emerging Priorities in Compounded Preparations for Children.
The problems related to pediatric pharmacotherapeutics and medication management are not unique to any particular country, as drug therapy problems are common causes of emergency department visits. Over the past 20 years, there were only sporadic scientific and commercial efforts to develop unique oral nonsterile dosage forms with a potential for mass production and standardization that would address the needs of pediatric patients under the age of four years with chronic diseases. This article raises awareness of the issues encountered in pharmacy pediatrics practice surrounding compounded nonsterile preparations. Current trends and emerging priorities at the interface between the use of these preparations and patient safety will be discussed. Trends in compounded nonsterile preparations preparation for children include standardization of nomenclature, formulation, dose, re-purposing old medications, reformulating older drugs, increasing federal oversight of pharmacy compounding, and changes to broaden the scope of indications in the product's label. Among the emerging priorities for safe pediatric compounded nonsterile preparations use include creation of new formulations for expanding pediatric diagnoses, improved quality-control processes described in United States Pharmacopeia Chapter <795>, closing the patient safety gap with changes to the prescription fulfillment systems, and employment of board-certified pediatric pharmacy specialists within the fulfillment process. In particular, an emerging opportunity to close the good clinical practice-good manufacturing practice gap at the pharmacy or point-of-care level with application of reverse-engineering concepts and other novel solutions have the potential to improve a pharmacist's ability to produce quality pediatric compounded nonsterile preparations. A systems approach (Formulation, Information, Collaboration, and Innovation) to the design of an integrated prescription generation and medication management system for children, including a simulation functionality, would include validation of small batch compounded nonsterile preparations, provision of complete information necessary to verify a prescription order, establishment of models of collaboration between board-certified pediatric clinical pharmacists and pediatricians, and performance of pragmatic clinical trials regarding compounded nonsterile preparation use in children.


Aetiology of convulsions due to stellate ganglion block: a review and report of two cases.
Stellate ganglion block is a selective sympathetic block that affects the ipsilateral head, neck, upper extremity and upper part of the thorax. Convulsions are a recognized complication of intra-arterial injection during stellate ganglion block. As central nervous system toxicity depends ultimately on the concentration of the local anaesthetics presented to the brain, the likely causative factors are discussed as well as the types of toxic symptoms and their onset times. The paper considers the aetiological factors of such convulsions resulting from stellate ganglion block in two patients.


Empirically derived subgroups in rheumatoid arthritis: association with single-nucleotide polymorphisms on chromosome 6.
Rheumatoid arthritis (RA) is a disorder with important public health implications. It is possible that there are clinically distinctive subtypes of the disorder with different genetic etiologies. We used the data provided to the participants in the Genetic Analysis Workshop 15 to evaluate and describe clinically based subgroups and their genetic associations with single-nucleotide polymorphisms (SNPs) on chromosome 6, which harbors the HLA region. Detailed two- and three-SNP haplotype analyses were conducted in the HLA region. We used demographic, clinical self-report, and biomarker data from the entire sample (n = 8477) to identify and characterize the subgroups. We did not use the RA diagnosis itself in the identification of the subgroups. Nuclear families (715 families, 1998 individuals) were used to examine the genetic association with the HLA region. We found five distinct subgroups in the data. The first comprised unaffected family members. Cluster 2 was a mix of affected and unaffected in which patients endorsed symptoms not corroborated by physicians. Clusters 3 through 5 represented a severity continuum in RA. Cluster 5 was characterized by early onset severe disease. Cluster 2 showed no association on chromosome 6. Clusters 3 through 5 showed association with 17 SNPs on chromosome 6. In the HLA region, Cluster 3 showed single-, two-, and three-SNP association with the centromeric side of the region in an area of linkage disequilibrium. Cluster 5 showed both single- and two-SNP association with the telomeric side of the region in a second area of linkage disequilibrium. It will be important to replicate the subgroup structure and the association findings in an independent sample.


Interplay of carriers and deep-level recombination centers of 275-nm light-emitting diodes - Analysis on the parasitic peaks over wide ranges of temperature and injection density.
The low luminance efficiency, poor reliability and parasitic peaks have greatly limited the commercialization of deep ultraviolet (DUV) light-emitting diodes. Tasks of identifying the culprits of these deficits are of paramount importance but remains unaccomplished. We employ the full-range temperature (20 K -300 K) measurement on 275-nm DUV devices that subjected to a 15-hour current-stress aging. The results suggest that the primary culprit of fast luminous decay is the proliferation of non-radiative centers. The origins of two main parasitic peaks are identified. The 310-nm peak is considered to solely come from deep-level radiative centers (DLRCs) that only dwell in the active region. Whereas, the 400-nm peak is proven to be dual-sources. One is related to the DLRCs in the active region, which only can be observed at very low currents; the other emerging at higher currents are associated with similar kinds of DLRCs located in the p-region, which only are excited when electrons overflow. This new discovery also demonstrates that a thorough investigation on the interplay among carriers and various types of defects should be conducted on the basis of the measurement that is taken under a wide temperature range, as well as under a proper forward voltage. This is to let the quasi-Fermi level shift across deep defect levels, the band-edge, and to over-band, whereby these recombination sites are exposed to deficit, moderate and saturated electron environment so that their natures can be well tested.


A Review on Bioactive Compounds, Ethnomedicinal Importance and Pharmacological Activities of Talinum triangulare (Jacq.) Willd.
Talinum triangulare (Jacq.) Willd. is a traditional leafy vegetable used by tribal communities for ethnomedicinal and ethnoculinary preparations. This article reviews the current knowledge of its multiple uses, including pharmacological activities and nutritional composition. The literature survey shows that it has been traditionally useful in the treatment of several diseases, such as anaemia, diabetes, measles, and ulcers and the preparation of various traditional foods. Analysis of the literature on its phytochemicals shows its richness in bioactive compounds. Further, research also shows that this plant has antidiabetic, antiobesity, antitumor, antiulcer, hepatoprotective, and neuroprotective activities besides anti-inflammatory and antioxidant properties. Nutrient analysis of the plant reveals the presence of Ca, Zn, Fe, vitamins C and E, dietary fibre and protein in considerable quantities. The results of the pharmacological studies on the antidiabetic, antiulcer and anti-anaemic activities provide support in favour of its ethnomedicinal uses. The presence of bioactive compounds and pharmacological activities show the usefulness of this plant as a functional food.


Redox regulation of the influenza hemagglutinin maturation process: a new cell-mediated strategy for anti-influenza therapy.
The aim of this study was to determine whether GSH-C4, a hydrophobic glutathione derivative, affects in vitro and in vivo influenza virus infection by interfering with redox-sensitive intracellular pathways involved in the maturation of viral hemagglutinin (HA). GSH-C4 strongly inhibited influenza A virus replication in cultured cells and in lethally infected mice, where it also reduced lung damage and mortality. In cell-culture studies, GSH-C4 arrested viral HA folding; the disulfide-rich glycoprotein remained in the endoplasmic reticulum as a reduced monomer instead of undergoing oligomerization and cell plasma-membrane insertion. HA maturation depends on the host-cell oxidoreductase, protein disulfide isomerase (PDI), whose activity in infected cells is probably facilitated by virus-induced glutathione depletion. By correcting this deficit, GSH-C4 increased levels of reduced PDI and inhibited essential disulfide bond formation in HA. Host-cell glycoprotein expression in uninfected cells was unaffected by glutathione, which thus appears to act exclusively on glutathione-depleted cells. All currently approved anti-influenza drugs target essential viral structures, and their efficacy is limited by toxicity and by the almost inevitable selection of drug-resistant viral mutants. GSH-C4 inhibits influenza virus replication by modulating redox-sensitive pathways in infected cells, without producing toxicity in uninfected cells or animals. Novel anti-influenza drugs that target intracellular pathways essential for viral replication ("cell-based approach") offer two important potential advantages: they are more difficult for the virus to adapt to and their efficacy should not be dependent on virus type, strain, or antigenic properties. Redox-sensitive host-cell pathways exploited for viral replication are promising targets for effective anti-influenza strategies.


CD98hc (SLC3A2) interaction with beta 1 integrins is required for transformation.
CD98hc (SLC3A2) constitutively and specifically associates with beta(1) integrins and is highly expressed on the surface of human tumor cells irrespective of the tissue of origin. We have found here that expression of CD98hc promotes both anchorage- and serum-independent growth. This oncogenic activity is dependent on beta(1) integrin-mediated phosphoinositol 3-hydroxykinase stimulation and the level of surface expression of CD98hc. Using chimeras of CD98hc and the type II membrane protein CD69, we show that the transmembrane domain of CD98hc is necessary and sufficient for integrin association in cells. Furthermore, CD98hc/beta(1) integrin association is required for focal adhesion kinase-dependent phosphoinositol 3-hydroxykinase activation and cellular transformation. Amino acids 82-87 in the putative cytoplasmic/transmembrane region appear to be critical for the oncogenic potential of CD98hc and provide a novel mechanism for tumor promotion by integrins. These results explain how high expression of CD98hc in human cancers contributes to transformation; furthermore, the transmembrane association of CD98hc and beta(1) integrins may provide a new target for cancer therapy.


Liquid chromatography-tandem mass spectrometry method for simultaneous quantification of azoxystrobin and its metabolites, azoxystrobin free acid and 2-hydroxybenzonitrile, in greenhouse-grown lettuce.
Lettuce is an important part of the diet in Europe. The permitted levels of pesticides in lettuce are strictly regulated and there is growing urge among food safety authorities to analyse pesticide metabolites as well. Azoxystrobin is one of pesticides that is frequently detected in lettuce. Although there are several analytical methods for the determination of azoxystrobin in lettuce, a sensitive method for the determination of its metabolites in lettuce is lacking. This study aimed at developing an extraction and LC-MS/MS method for the simultaneous determination of azoxystrobin, and its metabolites azoxystrobin free acid and 2-hydroxybenzonitrile in lettuce. Accelerated solvent extraction, QuEChERS extraction, and shaking extraction were compared using various solvents. The final method consisted of shaking freeze-dried sample in 0.1% formic acid in 80% aqueous acetonitrile. The selected method was validated by spiking each analyte at 125 ng/g and 500 ng/g. The method resulted in acceptable recovery for 2-hydroxybenzonitrile, azoxystrobin free acid, and azoxystrobin, with a RSD of <10%. The matrix-matched calibration curve for each analyte was linear over the range of quantification, with a correlation coefficient ≥0.98. The method was sensitive for the determination of 2-hydroxybenzonitrile, azoxystrobin free acid, and azoxystrobin, with limits of quantification of 0.36, 0.48, and 0.68 ng/g dry weight, respectively. The method was successfully applied to quantify 2-hydroxybenzonitrile, azoxystrobin free acid, and azoxystrobin in greenhouse-grown lettuce.


Chicken embryo as an experimental model for the study of gastroschisis.
To reproduce the experimental model of gastroschisis in chicken embryos and to prove that the histopathological changes that occur in this model can be compared to those in human gastroschisis. A total of 278 Leghorn hen (Gallus domesticus) eggs were used. The embryos were divided into three groups: the gastroschisis group, in which the umbilical cord was opened through an orifice made in the eggshell, and the intestinal loops were exposed to a mixture of amniotic liquid and allantoid; the mixture group, in which the amniotic fluid and allantoid were simply mixed without manipulating the umbilical stump and without exposing intestinal loops; and the control group which consisted of normal embryos in which no procedure was performed. The procedures were performed on the 13th day of embryo development and the study ended on the 19th day, when the intestinal loops of the embryos were removed and sent for conventional histological study and digital morphometric analysis. At the end of the experiment, 23 live embryos were obtained in the gastroschisis group (11.1% survival), and 18 of these presented exposed intestinal loops (8.7% success). The embryos of the gastroschisis group weighed less than those of the other two groups. The gastroschisis group also developed intestinal changes consisting of the thickening of the intestinal wall, inflammatory infiltration of the serosa and mucosa, ischemic changes in the intestinal wall and formation of a fibrin layer over the loops. These findings are characteristic of human gastroschisis and were not observed in the two other groups studied. The experimental model in chicken embryos proved able to reproduce the intestinal changes of human gastroschisis.


New approach in features extraction for EEG signal detection.
This paper describes a new approach in features extraction using time-frequency distributions (TFDs) for detecting epileptic seizures to identify abnormalities in electroencephalogram (EEG). Particularly, the method extracts features using the Smoothed Pseudo Wigner-Ville distribution combined with the McAulay-Quatieri sinusoidal model and identifies abnormal neural discharges. We propose a new feature based on the length of the track that, combined with energy and frequency features, allows to isolate a continuous energy trace from another oscillations when an epileptic seizure is beginning. We evaluate our approach using data consisting of 16 different seizures from 6 epileptic patients. The results show that our extraction method is a suitable approach for automatic seizure detection, and opens the possibility of formulating new criteria to detect and analyze abnormal EEGs.


Treatment outcome for head and neck squamous cell carcinoma in a developing country: University Malaya Medical Centre, Malaysia from 2003-2010.
Head and neck cancer (HNC) is the eighth most common cancer as estimated from worldwide data. The incidence of HNC in Peninsular Malaysia was reported as 8.5 per 100,000 population. This study was aimed to determine the treatment outcomes for HNC patients treated in the Oncology Unit of University Malaya Medical Centre (UMMC). All newly diagnosed patients with squamous cell carcinoma of head and neck (HNSCC) referred for treatment to the Oncology Unit at UMMC from 2003-2010 were retrospectively analyzed. Treatment outcomes were 5-year overall survival (OS), cause specific survival (CSS), loco-regional control (LRC) and radiotherapy (RT) related side effects. Kaplan-Meier and log rank analyses were used to determine survival outcomes, stratified according to American Joint Committee on Cancer (AJCC) stage. A total of 130 cases were analysed. Most cases (81.5%) were at late stage (AJCC III-IVB) at presentation. The 5-year OS for the whole study population was 34.4% with a median follow up of 24 months. The 5-year OS according to AJCC stage was 100%, 48.2%, 41.4% and 22.0% for stage I, II, III and IVA-B, respectively. The 5-year overall CSS and LCR were 45.4% and 55.4%, respectively. Late effects of RT were documented in 41.4% of patients. The most common late effect was xerostomia. The treatment outcome of HNSCC at our centre is lagging behind those of developed nations. Efforts to increase the number of patients presenting in earlier stages, increase in the use of combined modality treatment, especially concurrent chemoradiotherapy and implementation of intensity modulated radiotherapy, may lead to better outcomes for our HNC patients.


A new large species of gecko of the genus Hemidactylus Oken, 1817 (Reptilia: Sauria: Gekkonidae) from the Eastern Ghats, India.
A new large species of gecko superficially resembling Hemidactylus maculatus Duméril & Bibron and its allied large Hemidactylus is described from Eastern Ghats. The new species, Hemidactylus kangerensis sp. nov. can be easily distinguished from members of the H. maculatus complex based on the number of femoral pores, i.e. 18-21 on each side, separated medially by 4 non-pored scales. A phylogenetic analysis based on partial sequence of mitochondrial gene cytochrome b shows that the gecko is a member of the "H. prashadi" clade and is sister to H. maculatus, from which it differs in an uncorrected pairwise sequence divergence of 10%. The discovery of a new large gecko from Eastern Ghats advocates the need for biodiversity assessment across the neglected Eastern Ghats.


One-pot synthesis of nitrones from primary amines and aldehydes catalyzed by methyltrioxorhenium.
One-pot condensation/oxidation of primary amines and aldehydes using urea-hydrogen peroxide (UHP) as the stoichiometric oxidant in the presence of methyltrioxorhenium (MTO) as catalyst affords nitrones in a simple and regioselective manner. UHP is a practical and safe source of H2O2, and its use here instead of aqueous H2O2 solutions also simplifies greatly the workup procedure as extractions with organic solvents can be avoided. Typically, at the end of the reaction the solid urea is simply filtered off. From a sustainability point of view, this one-pot synthesis is simple to perform, takes place under mild conditions, has a high atom economy, and releases water as the only by-product.


Neonatal ovarian torsion complicated by intestinal obstruction and perforation, and review of the literature.
We present a case of neonatal ovarian torsion complicated by bowel obstruction and perforation and review the literature regarding the incidence of bowel obstruction in neonatal ovarian cysts, the presentation, and treatment. A term neonate was prenatally diagnosed with a cystic abdominal mass palpable on physical examination. A postnatal abdominal x-ray showed paucity of gas in the left hemiabdomen with rightward displacement of bowel loops. Exploratory laparotomy on day 2 of life revealed a large cystic mass in the left lower quadrant consistent with a torsed left ovary, an omental band causing strangulation of the bowel mesentery, and a perforation of the distal ileum. Our literature search revealed 19 reported cases of neonatal ovarian cysts resulting in bowel obstruction. Infants may present with a palpable abdominal mass, respiratory distress, as well as signs and symptoms of intestinal obstruction. Two mechanisms exist for bowel obstruction: adhesions caused by a torsed necrotic ovary and mass effect of a large ovarian cyst, often measuring 9 to 10 cm in diameter. Options to treat ovarian cysts include antenatal or postnatal aspiration, laparoscopy, and laparotomy. Cysts less than 4 to 5 cm can be observed, whereas operative intervention is indicated in symptomatic cases and in persistent or enlarging ovarian cysts.